Platinum resistance induces diverse evolutionary trajectories in high grade serous ovarian cancer
Hoare, J. I.; Hockings, H.; Saxena, J.; Silva, V. L.; Maniati, E.; Mirza, H. B.; Huang, W.; Wood, G. E.; Nicolini, F.; Graham, T. A.; McNeish, I. A.; Lockley, M.
Show abstract
Resistance to therapy is an enduring challenge in cancer care. Here we interrogate this critical unmet need using high grade serous ovarian cancer (HGSC) as a disease model. We have generated a unique panel of platinum-resistant HGSC models and shown that they share multiple transcriptomic features with relapsed human HGSC. Moreover, they evolve diverse in vivo phenotypes reflecting the human disease. We previously characterised copy number signatures in HGSC that correlate with patient survival and now provide the first evidence that these signatures undergo recurrent alterations during platinum therapy. Furthermore, specific, resistance-associated signature change is associated with functionally relevant gene expression differences. For example, reduced signature 3 (BRCA1/2-related homologous recombination deficiency) is associated with increased expression of homologous recombination repair genes (Rad51C, Rad51D, BRCA1) and DNA recombination pathway enrichment. Our mechanistic examination therefore provides new and clinically relevant insights into the genomic evolution of platinum-resistant cancers.
Matching journals
The top 9 journals account for 50% of the predicted probability mass.
Similar papers in this journal
- Bypassing cisplatin resistance in Nrf2 hyperactivated head and neck cancer through effective PI3Kinase targeting 95%
- Sequential ATR and PARP Inhibition Overcomes Acquired DNA Damaging Agent Resistance in Pancreatic Ductal Adenocarcinoma 94%
- Pro-survival roles for p21(Cip1/Waf1) in Non-Small Cell Lung Cancer 93%
Similar papers in this journal
- Ovarian cancers with low CIP2A tumor expression constitute an APR-246 sensitive disease subtype 95%
- Clinical positioning of the IAP antagonist tolinapant (ASTX660) in colorectal cancer 95%
- Small molecule mediated stabilization of PP2A modulates the Homologous Recombination pathway and potentiates DNA damage-induced cell death 94%
Similar papers in this journal
- The MEK1/2 pathway as a therapeutic target in high-grade serous ovarian carcinoma 95%
- HIF-dependent expression of creatine kinase brain isoform (CKB) promotes breast cancer metastasis, whereas cyclocreatine therapy impairs invasion and improves the efficacy of conventional chemotherapies 94%
- An inducible BRCA1 expression system with in vivo applicability uncovers activity of the combination of ATR and PARP inhibitors to overcome therapy resistance 94%
Similar papers in this journal
- Kinome focused CRISPR-Cas9 screens in African ancestry patient-derived breast cancer organoids identifies essential kinases and synergy of EGFR and FGFR1 inhibition. 95%
- Biomarker-guided treatment strategies for ovarian cancer identified from a heterogeneous panel of patient-derived tumor xenografts 94%
- Modeling High-grade serous ovarian carcinoma using a combination of in vivo electroporation and CRISPR/Cas9 mediated genome editing 94%
Similar papers in this journal
- Long-term patient-derived ovarian cancer organoids closely recapitulate tumor of origin and clinical response 95%
- ROLE OF cfDNA AND ctDNA TO IMPROVE THE RISK STRATIFICATION AND THE DISEASE FOLLOW-UP IN PATIENTS WITH ENDOMETRIAL CANCER: TOWARDS THE CLINICAL APPLICATION 95%
- FSTL3 is a biomarker of poor prognosis and is associated with immunotherapy resistance in ovarian cancer. 94%
"Similar papers" are the closest papers from that journal in the model's embedding space. They show what the match is built on, but the ranking comes mostly from a classifier over the whole training set, not from these examples alone.